This invention relates to novel pyrazole compounds having valuable pharmacological properties and to their preparation and use. In particular, the invention is concerned with a series of new 1H-substituted arylpyrazole derivatives which are inhibitors of blood platelet aggregation.
Various derivatives of tetrahydroimidazo[2,1-b]quinazolin-2-one and 2,3-dihydro-2-oxo-imidazo[4,5-b]quinolin-2-one have been described and shown to be useful as blood platelet antiaggregative and cardiotonic agents. Representative examples of these two classes are:
Chodnekar et al., U.S. Pat. No. 4,256,748, issued on Mar. 17, 1981, describes a series of compounds having the formula ##STR3## Representative of the Chodnekar compounds are RO 15-2041 (R.sup.4 .dbd.CH.sub.3, R.sup.3 .dbd.H, R.sup.2 .dbd.6-CH.sub.3, R.sup.1 .dbd.7-Br) and RO 13-6438 (R.sup.4 .dbd.CH.sub.3, R.sup.3 .dbd.H, R.sup.2 .dbd.6-CH.sub.3, R.sup.1 .dbd.H).
Meanwell et al., U.S. Pat. No. 4,668,686, issued on May 26, 1987, describes a series of compounds having the formula ##STR4## Representative of the Meanwell compounds is BMY-20844 wherein R.sup.1 .dbd.H, R.sup.2 .dbd.7-CH.sub.3, R.sup.3 .dbd.8-CH.sub.3 and R.sup.4 .dbd.H.
A different class of compounds from those described above are a series of substituted imidazol-2-yl alkanoic acid derivatives which are reported to be useful as antithrombotic, anti-inflammatory, antiatherosclerotic and lipid lowering agents.
Lautenschlager et al., in U.S. Pat. No. 4,460,598 issued July 17, 1984 describes a series of triphenylimidazol-2-yloxyalkanoic acids having the formula ##STR5## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 each are H, halogen, alkyl, alkoxy and trifluoromethyl; n is an integer of 1 to 10 and R.sup.7 is H, alkali metal ions, alkyl or benzyl group. A particularly preferred member of the series wherein R.sup.1 to R.sup.6 is hydrogen, n is 7 and R.sup.7 is sodium, is identified in the art as octimibate sodium and has been studied extensively, for example, Lautenschlager et al., Drugs of the Future, 1986; 11(1), 26; Ibid. 1987; 12, 84; Ibid. 1988; 13(1), 81. Although octimibate is described as possessing anti-aggregatory activity, it is being developed in man as an antihyperlipidemic agent.
German Patent applications DE-3,504,677, 3,504,678, 3,504,679 and 3,504,680 all published on Aug. 14, 1986, and European Patent Application EP-130,526, published on Sept. 1, 1985, describe a large number of substituted imidazol-2-yl derivatives similar to the above-mentioned U.S. Pat. No. 4,460,598.
European Patent Application EP-248,594, published on Dec. 9, 1987, describes a series of 1,5-Diphenyl-3-substituted pyrazole compounds of formula ##STR6## wherein Y is H, Br, Cl, or lower alkyl; R is C.sub.2-16 optionally unsaturated straight chain hydrocarbon group and R.sup.1, R.sup.2, R.sup.3, R.sup.4 and X represent various substituents. These compounds are reported to inhibit cyclooxygenase and/or lipoxygenase pathway(s) and are useful for alleviating inflammation, asthma, hypersensitivity, myocardial ischaemia, dermatological conditions and gastrointestinal inflammatory conditions.